In vitro studies provide important information on the release, intra-actions and storage of peptides by single cells or isolated organs. The results obtained from these studies must be extrapolated to the intact animal in order to more fully determine their physiologic relevance. The present proposal will use dogs and rats as animal models to conduct studies designed to test the hypothesis that digestive processes are brought about by the interaction between substances produced by the gastrointestinal tract, pancreas, and possibly the brain and that the role of a single peptide is downplayed by these interactions. This proposal is designed to test this hypothesis by investigating the crossreactivities, interactivities and bioactivities of gastrointestinal peptides by radioimmunoassay, bioassays, and chemical assay methods. Use of specific antisera is an excellent method for determining if a peptide is involved in a biologic action and to determine the role of a single peptide in the presence of the release of a cascade of peptides. Studies are planned, in dogs, to use specific antisera that have been generated against GI peptides to investigate the roles of these peptides singularly or in combinations or release, storage and biologic actions of GI peptides. Rhythm is a fundamental property of biologic entities. Studies will be conducted to determine in dogs the circadian (24 plus or minus 4 hr), circaseptan (7 plus or minus 3 days), circatrigintan (30 plus or minus 5 days) and circannual (12 plus or minus 2 mos.) variations of GI peptides in dogs and to determine whether or not these variations effect the biologic actions of peptides. Evidence is mounting that there are endocrinologic interactions between the pituitary, gonadal axis and the GI-pancreatic axis. Studies are planned to systematically investigate in rats the interrelationships between hormones of pituitary and gonadal origin and peptides of gastrointestinal and pancreatic origin. Evidence suggest that different operative procedures on, and resections of, different regions of the gastrointestinal tract affect release and actions of GI peptides as well as growth of remaining sections of the gut. The influence of resection of different regions of the gastrointestinal tract on the release, actions and morphology of GI peptides will be studied in dogs in order to establish more fully which and how different regions of the GI tract effect the normal endocrinologic functions of the entire GI tract. The successful completion of these studies should provide important information on the actions and interactions between peptides of GI, pancreatic and pituitary origin and gonadal steroids.